scholarly journals 86 GENETIC OVERLAP BETWEEN PSYCHOTIC EXPERIENCES IN THE COMMUNITY ACROSS AGE AND WITH PSYCHIATRIC DISORDERS

2019 ◽  
Vol 29 ◽  
pp. S107-S108
Author(s):  
Angelica Ronald ◽  
Wikus Barkhuizen ◽  
Oliver Pain ◽  
Frank Dudbridge
Keyword(s):  
Psychiatric Disorders ◽  
Psychotic Experiences ◽  
Genetic Overlap

scholarly journals Genome-wide analysis of adolescent psychotic experiences shows genetic overlap with psychiatric disorders

2018 ◽  
Author(s):  
Oliver Pain ◽  
Frank Dudbridge ◽  
Alastair G. Cardno ◽  
Daniel Freeman ◽  
Yi Lu ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depression ◽  
Psychiatric Disorders ◽  
Negative Symptoms ◽  
Genome Wide Association Study ◽  
Genetic Influences ◽  
Psychotic Experiences ◽  
Psychotic Experience ◽  
Genome Wide ◽  
Genetic Overlap

AbstractThis study aimed to test for overlap in genetic influences between psychotic experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic experience domain was performed. SNP-heritability of each psychotic experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium-(LD-) score regression. Genetic overlap between specific psychotic experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk scoring (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and major depression.

scholarly journals Genetic overlap and causal associations between smoking behaviours and psychiatric traits and disorders in adolescents and adults

2020 ◽  
Author(s):  
Wikus Barkhuizen ◽  
Frank Dudbridge ◽  
Angelica Ronald
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Structural Equation ◽  
Negative Symptoms ◽  
Genetic Correlations ◽  
Genetic Influences ◽  
Psychotic Experiences ◽  
Genetic Associations ◽  
Genetic Overlap ◽  
Smoking Behaviours

AbstractBackgroundEpidemiological research shows that smoking is associated with psychiatric disorders and psychotic experiences, even after controlling for confounds such as cannabis use and sleep problems. We investigated degree of genetic overlap and tested for causal associations between smoking and psychiatric traits and disorders using genetic data. We tested whether genetic associations existed beyond genetic influences shared with confounding variables.MethodsGenetic correlations were estimated with LD-score regression between smoking behaviours (N=262,990-632,802) and psychiatric disorders (schizophrenia, bipolar disorder and depression; N=41,653-173,005), psychotic experiences in adolescents (N=6,297-10,098) and adults (N=116,787-117,794) and adult schizotypy (N=3,967-4,057). Genomic Structural Equation Modelling was performed to explore the associations while accounting for genetic influences of confounders (cannabis and alcohol use, risk-taking and insomnia). Causal associations were tested using Generalized Summary-based Mendelian Randomization (GSMR).ResultsSignificant genetic correlations were found between smoking and psychiatric disorders (rg = .10 - .38) and adult PE (rg = .33 - .40). After accounting for covarying genetic influences, genetic associations between most smoking phenotypes and schizophrenia and depression remained but not between smoking behaviours and bipolar disorder or most psychotic experiences. GSMR results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences.ConclusionsPleiotropy between smoking behaviours and schizophrenia and depression exists beyond the common genetic basis of known confounders. Smoking also appears to be causally associated with psychiatric disorders and with cognitive PEs and negative symptoms during adolescence. Exploration of the biological links underlying smoking and psychiatric illness would be well-justified.

scholarly journals Genetic overlap and causal associations between smoking behaviours and mental health

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wikus Barkhuizen ◽  
Frank Dudbridge ◽  
Angelica Ronald
Keyword(s):  
Mental Health ◽  
Psychiatric Disorders ◽  
Risk Taking ◽  
Smoking Initiation ◽  
Causal Role ◽  
Genetic Influences ◽  
Psychotic Experiences ◽  
Genetic Associations ◽  
Genetic Overlap ◽  
Smoking Behaviours

AbstractCigarette smoking is a modifiable behaviour associated with mental health. We investigated the degree of genetic overlap between smoking behaviours and psychiatric traits and disorders, and whether genetic associations exist beyond genetic influences shared with confounding variables (cannabis and alcohol use, risk-taking and insomnia). Second, we investigated the presence of causal associations between smoking initiation and psychiatric traits and disorders. We found significant genetic correlations between smoking and psychiatric disorders and adult psychotic experiences. When genetic influences on known covariates were controlled for, genetic associations between most smoking behaviours and schizophrenia and depression endured (but not with bipolar disorder or most psychotic experiences). Mendelian randomization results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences, although not consistently across all sensitivity analyses. In conclusion, smoking and psychiatric disorders share genetic influences that cannot be attributed to covariates such as risk-taking, insomnia or other substance use. As such, there may be some common genetic pathways underlying smoking and psychiatric disorders. In addition, smoking may play a causal role in vulnerability for mental illness.

Computational Models of Learning Mechanisms in Psychosis

2017 ◽  
Author(s):  
Andreas Heinz
Keyword(s):  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Computational Models ◽  
The Self ◽  
Psychotic Experiences ◽  
Learning Mechanisms ◽  
Top Down ◽  
Bottom Up ◽  
Surrounding World

Psychotic experiences may best be described as an alteration in the self-ascription of thoughts and actions, which is associated with a profoundly altered experience of oneself and the surrounding world. Computational models of key symptoms of psychiatric disorders are discussed with respect to the attribution of salience and self-relatedness to otherwise irrelevant stimuli and the role of top-down modelling in the generation of delusions. Top-down and bottom-up approaches in understanding mental disorders and their computational models are compared and critically reflected.

P.169 Genetic overlap between somatic insulin-related and neuro-psychiatric disorders

2020 ◽  
Vol 40 ◽  
pp. S97-S98
Author(s):  
G. Fanelli ◽  
F. Barbara ◽  
W. De Witte ◽  
N.R. Mota ◽  
G. Poelmans ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Overlap

scholarly journals Recent advances in the understanding and management of bipolar disorder in adults

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2033 ◽  
Author(s):  
Janusz K. Rybakowski
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Recent Progress ◽  
Molecular Genetic ◽  
Mood Stabilizer ◽  
New Drugs ◽  
Specific Drug ◽  
Genetic Approach ◽  
The Past ◽  
Genetic Overlap

This article focuses on some aspects of recent progress in the neurobiology and treatment of bipolar disorder (BD) in adults. A molecular-genetic approach to the etiopathogenesis of the illness resulted in the findings of a genetic overlap between BD and other major psychiatric disorders. Furthermore, a poly-gene-environmental interaction in the development of the illness has been demonstrated. For the management of BD, new drugs with putative mood-stabilizing properties have been introduced in the past two decades. However, none of these can surpass lithium, the prototype mood-stabilizer, still considered the most specific drug for BD. Recent research on lithium, besides providing new data on the neurobiology of BD, has confirmed anti-suicidal, immunomodulatory, and neuroprotective properties of this drug.

scholarly journals The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank

2019 ◽  
Author(s):  
Judit García-González ◽  
Julia Ramírez ◽  
David M. Howard ◽  
Caroline H Brennan ◽  
Patricia B. Munroe ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Smoking Behaviour ◽  
Environment Interaction ◽  
Uk Biobank ◽  
Psychotic Experiences ◽  
Gene Environment Interaction ◽  
Gene Environment

ABSTRACTWhile psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n=2067), hallucinations (n=6689), and any psychotic experience (delusions or hallucinations; n=7803) in 144818 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in the UK Biobank participants to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were significantly associated with psychotic experiences (p<1.77×10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p<1.99×10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD(but not PRSSCZ) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p<0.0028). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

scholarly journals Dissecting the genetic overlap of education, socioeconomic status, and mental health

2020 ◽  
Author(s):  
F. R. Wendt ◽  
G. A. Pathak ◽  
T. Lencz ◽  
J. H. Krystal ◽  
J. Gelernter ◽  
...  
Keyword(s):  
Mental Health ◽  
Bipolar Disorder ◽  
Socioeconomic Status ◽  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Morphology ◽  
Genetic Overlap ◽  
Genome Wide Data

AbstractSocioeconomic status (SES) and education (EDU) are phenotypically associated with psychiatric disorders and behavior. It remains unclear how these associations influence the genetic risk for mental health traits and EDU/SES individually. Using information from >1 million individuals, we conditioned the genetic risk for psychiatric disorders, personality traits, brain imaging phenotypes, and externalizing behaviors with genome-wide data for EDU/SES. Accounting for EDU/SES significantly affected the observed heritability of psychiatric traits ranging from 2.44% h2 decrease for bipolar disorder to 29.0% h2 decrease for Tourette syndrome. Neuroticism h2 significantly increased by 20.23% after conditioning with SES. After EDU/SES conditioning, novel neuronal cell-types were identified for risky behavior (excitatory), major depression (inhibitory), schizophrenia (excitatory and GABAergic), and bipolar disorder (excitatory). Conditioning with EDU/SES also revealed unidirectional causality between brain morphology and mental health phenotypes. Our results indicate genetic discoveries of mental health outcomes may be limited by genetic overlap with EDU/SES.

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